tbuckley/cabot-search huggingface dataset:
Abstract 9991: Index Case of Prosthetic Mitral Valve Dehiscence Secondary to SARS CoV 2 Virus: Histopathologic Evidence of T-cell Mediated Injury
Authors: Moiz Ehtesham, Arshan Khan, Muhammad Asim Shabbir
Journal: Circulation (2022)

Introduction: SARS-Cov-2 virus has been shown to inflict damage on native cardiac valvular tissue. We present the index case of prosthetic mitral valve (MV) dehiscence secondary to SARS-Cov-2 virus as evidenced by histopathologic analysis of peri-valvular annular tissue . Case: 63-year-old male with history of MV replacement 2 years ago presented with complaint of dyspnea for 2 weeks. He was asymptomatic on a cardiology appointment a month ago and had an unremarkable transthoracic echocardiography (TTE) at that time. On arrival, he was hypoxic to 80% on room air and chest exam revealed bibasilar crackles. Complete blood count and electrolytes were within normal ranges. He tested positive for SARS-Cov-2 virus RNA and had a recent family history of COVID-19. Chest X-ray revealed bilateral pulmonary vascular congestion. He was given supplemental oxygen through nasal cannula with improvement in pulse oximetry. Repeat TTE revealed mitral paravalvular leak with suspicion for prosthetic dehiscence. Transesophageal echocardiogram showed multiple jets of severe paravalvular regurgitation and disruption of the MV apparatus. No vegetations were detected on echocardiography. He underwent a pre-operative right heart catheterization which confirmed severe MV regurgitation with pulmonary artery (PA) capillary wedge pressure of 45mmHg (Normal: &lt;12) and a PA pressure of 40mmHg (Normal:&lt;20). Intra-operatively, we found near-complete dehiscence of prosthetic MV with surrounding annular calcifications. Our patient underwent surgical MV replacement with a biosynthetic valve. Histopathologic analysis of the annular tissue revealed myxomatous degeneration and an inflammatory infiltrate of CD4 T helper cells consistent with subacute to chronic inflammation. Of note, neutrophils were not detected which usually signify acute bacterial endocarditis. Tissue and blood cultures remained sterile. Our patient improved hemodynamically after MV replacement and was discharged home in stable condition. Conclusion: We propose that SARS-Cov-2 virus may cause prosthetic MV dehiscence through CD4 T cell-mediated damage to annular tissue. Such cases would require surgical valve replacement to manage the resulting hemodynamic compromise.
Abstract 9947: Prospective Prediction of Left Atrial Flutter From Computer Simulation
Authors: Matthias Lange, Eugene Kwan, Robert Macleod, T J Bunch, Ravi Ranjan
Journal: Circulation (2022)

Introduction: Atypical left atrial flutter (ALAF) is often the result of ablation treatment for AF. Many patients report a reduction in quality of life from AF to ALAF. If pharmacological rate control fails additional ablation can provide solutions. However, success rates are low due to difficulties in mapping all potential flutters accurately. Hypothesis: LGE-MRI can inform computation simulation to predict all possible ALAF pathways and increase the information available to the electrophysiologist. Methods: Informed and consented patients scheduled for ALAF ablation received an MRA and LGE-MRI. Fig1. From the MRA the left atrial wall was segmented and registered to the LGE-MRI. Scar and gray areas were estimated by threshold segmentation. The threshold was calculated with the intensity value ratio. The information was integrated into a monodomain model. Ionic currents were modeled according to Courtemanche with a reduction of some conductance in fibrotic regions. To induce ALAF S1S2 pacing was done with an S1 cycle length of 600ms and S2 decreased from 250 to 170ms. Induction was tested at 10 different locations. Results were provided to the electrophysiologist. Results: Prospective prediction of the ALAF pathway for six patients was successful and the clinically observed flutter was predicted. Fig. 2) shows the value of the prediction, electroanatomic mapping was inconclusive even unable to exclude the right side. Ablation on the right side did not alter the flutter, but ablation near the mitral valve. Conclusions: We successfully predicted clinically observed ALAF pathways. The next step is to find ablation points for all predicted pathways.
Abstract 9930: Exercise-Induced ATP7A, A Cu Transporter for SOD3, Restores Endothelial Dysfunction in Type2 Diabetes via Cysteine Oxidation of Protein Kinase G
Authors: Sudhahar Varadarajan, Kareem Abdelsaid, Harriet Boatwright, Malgorzata McMenamin, Philip Eaton, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation (2022)

Background: Exercise training protects against type2 diabetes (T2D)-induced endothelial dysfunction which is mediated through eNOS uncoupling-induced O 2 -, but its underlying mechanisms are not fully understood. Cu transporter ATP7A is required for full activity of antioxidant Cu enzyme extracellular SOD (SOD3) that scavenges O 2 - to generate H 2 O 2 that has been proposed to function as a signaling molecule to mediate endothelium-dependent vasorelaxation (EDR) in T2D instead of nitric oxide (NO). However, role of ATP7A and its link with H 2 O 2 signaling in exercise-induced restoration of endothelial function in T2D is entirely unknown. Results: Here we show that ATP7A protein (49%), SOD3 activity (51%) and extracellular H 2 O 2 levels as well as EDR in blood vessels of high fat diet-induced T2D mice were significantly decreased compared to those of control C57Bl6 mice, which were restored by volunteer wheel exercise (2 weeks) or in T2D/ATP7A overexpressing mice. Of note, exercise-induced restoration of EDR in T2D mice was inhibited by PEG-catalase infusion or direct application of catalase to vessels, or in ATP7A dysfunctional ATP7A mut mice or T2D/SOD3 knockout (KO) mice, but not by eNOS inhibitor, L-NAME. This suggests that exercise-induced ATP7A-SOD3 axis-derived H 2 O 2 , but not eNOS/NO, plays a role in this effect. We then examined downstream targets of exercise-induced H 2 O 2 in blood vessels and found that protein kinase G (PKG)1α that is shown to be activated by exogenous H 2 O 2 via oxidation at Cys42 was sulfenylated (CysOH formed)(2.3-fold increase) in response to exercise in aorta of T2D, but not control, mice. This T2D-specific exercise-induced CysOH formaton of PKG1a in vascular tissue was inhibited by T2D/ ATP7A mut mice or T2D/SOD3 KO mice or PEG-catalase treatment. Functionally, “redox-dead” PKG1a Cys42Ser knock-in mutant mice blocked exercise-induced restoration of EDR in T2D, not control mice. Conclusion: Exercise-induced ATP7A promotes SOD3-mediated out-side in H 2 O 2 signaling, which contributes to restore EC dysfunction in T2D via PKG1α oxidation at Cys42.
Abstract 9912: Cardiac Events Among Amyotrophic Lateral Sclerosis Patients in the United States; a Fresh Perspective From the 2019 National Inpatient Sample
Authors: Kamleshun Ramphul, Renuka Verma, Nomesh Kumar, Yogeshwaree Ramphul, Komal Kumari, Shaheen Sombans, Stephanie G Mejias, Petras Lohana, Fnu Arti
Journal: Circulation (2022)

Introduction: Respiratory distress and complications are the leading causes of death among Amyotrophic Lateral Sclerosis (ALS) patients. However, several studies have reported multiple cardiovascular complications linked with heart rate and rhythm. We, therefore, aim to investigate cardiovascular involvement among ALS patients further. Methods: Data from the 2019 National Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ), and partners were analyzed to estimate the presence of multiple cardiovascular events in patients with a diagnosis of Amyotrophic Lateral Sclerosis in the United States via their respective ICD-10 codes. The risk of cardiopulmonary resuscitations and mortality rates were also estimated via multivariate regression models, accounting for different variables. Results: We identified 12,865 cases of ALS in the United States. Different cardiac arrhythmias were recorded, such as supraventricular tachycardia (2.1%), ventricular tachycardia (1.7%), ventricular fibrillation (0.2%), and paroxysmal atrial fibrillation (3.8%), and long QT syndrome (0.6%). Several cases of heart blocks were also observed as 0.4% had a first degree, 0.3% had a second degree, and 0.3% had third-degree atrioventricular blocks. 10.7% also had a diagnosis of heart failure, and 565 (4.4%) patients had an old myocardial infarct. Finally, we found 160 (1.2%) cases of cardiopulmonary resuscitation, which had a higher risk of occurring among diabetics (aOR 1.922, 95%CI 1.383-2.670, p&lt;0.01) and patients with hypertension (aOR 1.516, 95% CI 1.007-2.134, p=0.017), while it was less common among Females (aOR 0.527,95% CI 0.368-0.755, p&lt;0.01). The adjusted odds ratio of death in ALS patients with cardiopulmonary resuscitation was 14.910 (95% CI 9.760-22.78, p&lt;0.01). Conclusions: Several cardiac arrhythmias can be observed among ALS patients. Cardiopulmonary resuscitation has a poorer outcome, and physicians treating ALS patients should be advised to watch for early changes, which may help reduce the need for CPR.
Abstract 9997: Atrial Fibrillation and Supraventricular Tachycardia Are Predictors of Inpatient Mortality in Mechanically Ventilated Patients in the United States
Authors: Moiz Ehtesham, Arshan Khan, Maria Riasat, Muhammad Asim Shabbir
Journal: Circulation (2022)

Objective: Arrhythmias are a significant clinical challenge and can complicate hospital course for mechanically ventilated patients. We aimed to determine the burden of arrhythmias and their effect on inpatient outcomes in mechanically ventilated patients in the US. Methods: The national inpatient sample was retrospectively studied (2015-2019) to identify all mechanically ventilated patients aged &gt;17. We further identified the following arrhythmias within each admission: atrial fibrillation (AF), non-sustained ventricular tachycardia (NSVT), supra-ventricular tachycardia (SVT), atrioventricular block (AVB) and ventricular fibrillation (VF). Primary outcomes were inpatient mortality rate, hospital length of stay (LOS) and total cost for each type of arrythmia. Demographic (age, sex, race) and clinical information (history of hypertension, stroke, myocardial infarction, obesity) was recorded. Data was studied in STATA 15 and multivariate logistic regression was used to estimate adjusted odds ratios (AOR) reported with p-value (significance=&lt;0.05). Results: Our analysis included 1,745,867 weighted discharges of mechanically ventilated patients. Mean age was 65 years (56% male, 69% Caucasian). Most frequent arrythmia was AF (63% of all patients) and least common was AVB (11%). AF, VF, and SVT were associated with an increase in mortality (AOR: 3.52, 2.78, 1.45 respectively, p &lt; 0.001). NSVT, AF, and SVT were associated with an increase in hospital LOS of 4.5, 3.2, and 2.8 days respectively (AOR 3.31, 2.94, 1.75 respectively, p&lt;0.001). The adjusted inpatient cost was highest in patients with NSVT ($21,567, p&lt;0.05). AVB and NSVT were not associated with an increase in mortality (p&lt;0.05). On gender and race stratification, African American males had the highest mortality rate secondary to AF and VF (AOR: 3.54 and 4.21 respectively, p&lt;0.001). Conclusion: We demonstrate that atrial fibrillation, ventricular fibrillation, and SVT are independently associated with increased mortality in mechanically ventilated patients. We also show that NSVT is associated with increase in hospital LOS in these patients. African American mechanically ventilated males had the highest mortality rates secondary to atrial and ventricular fibrillation.
Abstract 9929: Epigenome-Wide-Association-Study Characterizes DNA Methylation Changes Associated With Lung and Right Ventricle Dysfunction in Pulmonary Hypertension
Authors: Francois Potus, Nabil Azhar, EL-Kabbout Reem, Sandra Breuils Bonnet, Sandra Martineau, Vinod Krishna, Shanker Kalyana-Sundaram, Lysanne Girard, Victoria M Toro, Olivier Boucherat, Fany Guerra Bonilla, David Gutstein, Steeve Provencher, Jey R JEYASEELAN, Sebastien Bonnet
Journal: Circulation (2022)

Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy associated with pulmonary arteries remodeling and right ventricle (RV) dysfunction. Epigenetic dysregulation, including altered DNA methylation (DNAm), promotes PAH. However, the DNAm changes associated with PAH remain unexplored in human PAH RV and lungs. We conducted an exploratory study using human lung and RV samples to characterize the DNA methylome and transcriptomic changes associated with PAH. Methods/Results: We observed that PAH is associated with substantial changes in the DNAm landscape in both organs. We identified 88 identical differentially methylated probe (DMP) in both PAH Lungs and RV. Functionally, we observed that 65, and 76 of those DMP correlate with myocardial fibrosis and adverse pulmonary vascular remodeling, respectively. Then we clustered DMP onto functional differentially methylated region (DMR) and reported that 41% and 11.5% of the genes carrying a DMR are differentially expressed in PAH RV and lungs, respectively. Gene ontology analysis suggests that both impaired DNAm (DNA methylome) and genes expression (RNA sequencing) observed in PAH regulate biological functions related to inflammation, fibrosis, cell proliferation and vascular remodeling. Impaired DNAm landscape observed in PAH RV and lung is associated with the disease severity and contributes to 4.1% and 2.7% of the whole transcriptomic reprograming associated with PAH development in RV and lungs samples, respectively. Despite the modest overlap between DNAm and transcriptomic changes, we observed that DNAm affects genes and molecular pathways involved in PAH development. Conclusion: Although exploratory, our study is the first to characterize the DNAm and transcriptomic change associated with PAH in human RV and lung. Our data suggest that impaired DNAm landscape might contribute to the disease development/severity.
Abstract 9899: Effects of Ambient Air Pollutants on Progression of Cardiac Structure and Function in the Echocardiographic Study of Latinos (Echo-SOL)
Authors: Claire L Leiser, Daniela Sotres-Alvarez, Elizabeth W Spalt, Barry E Hurwitz, Martha L Daviglus, Bonnie Shook-Sa, Carlos J Rodriguez, Joel D Kaufman
Journal: Circulation (2022)

Background: Air pollutants may affect cardiac function; effects preceding clinical diagnosis of heart failure are not understood. We assessed longitudinal associations between fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ) and cardiac structure and function among 1,660 participants in the Echocardiographic Study of Latinos, in the Hispanic Community Health Study/Study of Latinos. Hypothesis: Air pollution is associated with longitudinal changes in subclinical structure/function. Methods: Left ventricular (LV) mass index, relative wall thickness, average global longitudinal strain (GLS), LV ejection fraction, e’, left atrial (LA) volume index, E/e’ ratio, and diastolic function grades were assessed by echocardiogram. Air pollution concentrations were estimated from validated spatio-temporal models at home locations, as mean concentrations of PM 2.5 and NO 2 for the year prior to clinical visit 1 (V1, 2008-2011) and 2 (V2, 2015-2018). A mixed effects model was used to jointly model cross-sectional and longitudinal relationships between time-varying air pollution and continuous measures of CF, adjusted for baseline physical activity, gender, education, age, BMI, SBP, DBP, statin use, diabetes, and hypertension status and time-varying smoking and alcohol use, with random intercepts for clinical center and primary sampling unit. Results: Participants’ mean age was 56.4 years at V1; mean follow-up was 6.52 years. Mean PM 2.5 was 10.3 μg/m 3 at V1 and 8.8 μg/m 3 at V2. Mean NO 2 was 17.4 ppb at V1 and 14.3 at V2. Per interquartile range of pollutant, higher PM 2.5 and NO 2 were associated with a 0.52% (95% CI -0.16, 1.11) and 0.98% (95% CI 0.13, 1.23) increase in GLS, respectively. NO 2 was associated with -1.07% (95% CI -2.24, 0.10) decrease in LV ejection fraction. PM 2.5 was associated with a 0.75 (95% CI 0.39, 1.12) increase in e’ and a 1.25 (95% -1.95, -0.56) decrease in E/e’ ratio. No other associations with air pollution and echo measures were found. Conclusion: These findings suggest that air pollution is associated with longitudinal changes in GLS, LV ejection fraction, e’, and E/e’ ratio in a US Hispanic/Latino cohort, an important understudied population. Air pollution may represent a modifiable risk factor in the development of clinical heart failure.
Abstract 9957: Utility of Cardiac MRI Assessment of Right Ventricle Function Before LVAD Implantation
Authors: Dae H Lee, Syed Imran Zaidi, Chinedu Madu, christopher scoma, Ronak Chhaya, Jason Feliberti, Benjamin Mackie, Aarti Patel, NIDHI PATEL
Journal: Circulation (2022)

Introduction: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a feared complication. Right ventricle (RV) dysfunction by echocardiogram prior to LVAD implant is a significant risk factor for post-LVAD RVF. However, RV’s unique crescent shape makes it difficult for accurate assessment through echocardiogram. Cardiac MRI can image RV in its entirety and is the gold standard for evaluating RV size and function. Hypothesis: Our study aimed to assess RV comprehensively through cardiac MRI before LVAD implantation to predict severe RVF post-LVAD. Methods: This retrospective cohort study included 231 consecutive patients who underwent LVAD from January 2015 to July 2021. We utilized the commercially available QStrain Application (Medis Suite, the Netherlands) for feature-tracking myocardial strain using gated cine SSFP images. We also assessed for quantitative measurements of RV (systolic/ diastolic volume, stroke volume, and systolic function). Results: There were 12 patients with cardiac MRI before LVAD, of which 4 patients developed severe RVF after LVAD. There were 9 cardiac MRIs available for strain analysis (image quality and old studies before 2012). The RV end-systolic volume (ESV) was higher in severe RVF post-LVAD, but not RV ejection fraction. Endocardial and myocardial global longitudinal strain and global radial strain of RV were not different in severe RVF. Conclusions: In this small series investigating RV function before LVAD implant, we have shown that ESV was higher with severe RVF. Although feature tracking strain of RV was not different in patients with severe RVF, a larger cohort study is warranted to investigate this.
Abstract 9928: Risk Stratification for Amputation in Patients With Symptomatic Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD
Authors: R. Wilson King, Mark R Nehler, Manesh R Patel, Sebastian Debus, Sonia S Anand, Mario Enrico Canonico, Cullen Buchanan, Warren Capell, Connie N Hess, Joseph Ycas, Judith A Hsia, Eva Muehlhofer, Lloyd P Haskell, Scott D Berkowitz, Rupert Bauersachs, Marc P Bonaca
Journal: Circulation (2022)

Introduction: Amputation is a severe consequence of peripheral artery disease (PAD), and systems for risk stratification have been developed. The performance of these systems in trials of PAD patients after successful lower extremity revascularization (LER) and receiving modern medical therapies has not been well described. Hypothesis: Risk of amputation is associated with the Rutherford Chronic Limb Ischemia class as well as the wound, ischemia, and foot infection (WIfI) grade in patients with PAD after LER. Methods: Patients in the VOYAGER PAD trial were assigned a Rutherford class at baseline and follow up. A WIfI score was assigned by 2 vascular specialists blinded to outcome and treatment allocation. Incidence of the composite of first major or minor amputation through 3 years were calculated by risk group. Results: Of 6,564 randomized, Rutherford was available in 6543 and WIfI in 6471. Due to the trial’s inclusion criteria, no Rutherford 6/WIfI high risk were included. Despite successful LER, there was a stepwise increase in the risk of amputation (p&lt;.001) with increasing baseline Rutherford classification (Figure 1A) with incidence at 3 years of 22.4% in Rutherford 5. Risk was also associated with WIfI (Figure 1B); however, those classified as “very low” risk still a 15% incidence of amputation. When stratified by diabetes mellitus (DM), those with DM were at higher risk in all WIfI classes. Those with DM classified as "very low" risk had a higher incidence of amputation than patients without DM stratified as “moderate risk”. Conclusions: In a large clinical trial of patients with symptomatic PAD post successful LER, high incidences of amputation were observed despite contemporary medical therapies. In patients eligible for the study, Rutherford and WIfI both stratify risk; however, those with WIfI “very low” risk still had high incidences of amputation. Risk in those with DM was higher in each WIfI class suggesting that this could be considered in risk stratification.
Abstract 9900: Virtual Simulation-Based CME Improves Management of Patients With Vascular Disease
Authors: Margaret Harris, Michael Lacouture, Catherine Capparelli, Bonaca Marc, Joshua Beckman, Herbert D Aronow
Journal: Circulation (2022)

Introduction: The ability of virtual patient simulation (VPS) case-based interventions to improve clinical decision making for patients with peripheral artery disease (PAD) is unknown. Methods: Two patient cases were presented using a VPS platform where learners could order tests, make diagnoses, and order treatments in a manner matching the scope and depth of actual practice. Clinical decisions were analyzed, and learners received clinical guidance (CG) based on current evidence and expert recommendations. Learners could modify their decisions post-CG. Pre-(baseline) vs. post-CG decisions were compared using McNemar’s test. The intervention launched on July 30, 2021, and data were collected through October 13, 2021. Results: Overall, 143 physicians participated (76 case 1, 67 case 2). Physician specialties included cardiology (74%), and vascular surgery (26%). Most physicians were male (62%) with the following age distribution &lt; 30 (8%), 30-39 (25%), 40-49 (19%), 50-59 (17%), and ≥ 60 (31%). Significant improvements were seen for appropriate diagnosis and treatment selection in the overall learner population; treatment improvements were greatest for tailoring antithrombotic therapy in patients with newly diagnosed PAD ( Table ). Improvements in selection of appropriate antithrombotic treatment were observed for all specialties, although specialty-specific differences were apparent ( Table ). Conclusions: Case-based PAD intervention employing VPS was associated with improvements in diagnostic and therapeutic decision-making among cardiologists and vascular surgeons. Despite the observed improvements, gaps remain in diagnosing and selecting appropriate antithrombotic strategies for patients with PAD.